The objective of this research is to understand in detail the mechanisms by which mammalian cells repair ionizing radiation damage in their DNA. Relationships between the repair of lesions in DNA at the molecular level and cellular radiobiological phenomena which are believed to be important to human cancer radiotherapy (including the variation in sensitivity through the cell cycle, the oxygen effect, the increased effectiveness of high linear energy transfer (LET) radiation, the differences in radiosensitivity between tumor cells and normal cells) will be investigated. The experimental approaches to these questions will make use of several techniques which have become available in the last few years such as synchrony of mammalian cells by centrifugal elutriation and detection of strand breaks in DNA by alkaline elution. While these methodologies were originally developed for use on cultured mammalian cells, they have recently been modified so that cells from normal or tumor tissue may also be studied. Thus, the questions concerning the importance of DNA repair at the molecular level to radiobiological phenomena at the cellular level may now be addressed in the in vivo tumor situation. Ultimately, knowledge about these relationships may allow the design of radiotherapy modalities that take maximum advantage of radiobiological factors.